This is a renewal application to continue our ICBG efforts in Panama which combine the goals of drug discovery from natural sources with host country infrastructure development, training, economic growth, biodiversity inventories, and conservation. The past 4.5 years have been highly productive in all of these areas, with the majority of effort occurring in the host country and at host country institutions. Panama possesses an extraordinary biodiversity of plants and algae owing to its unique juxtaposition between North and South America and between the Caribbean Sea and the Pacific Ocean. As such, Panama is a "biodiversity hotspot" as well as a biological corridor between these major geographical features, thus providing unique opportunities for high impact regional and international conservation strategies. We have assembled a remarkable team from Panamanian and US academic institutions as well as leaders in the pharmaceutical and agrochemical industries. We propose a team effort to explore the natural products of diverse terrestrial plants, marine algae and cyanobacteria for compounds active to several tropical diseases, (leishmaniasis, Chagas' disease, and malaria) cancer (cell- and mechanism-based) and agricultural pests. Our ecological approach to selecting plants for collection, as well as a processing strategy, which preserves biologically active materials, yields a higher rate of active extracts than otherwise expected. Our conservation efforts involve leading institutions such as the Smithsonian Tropical Research Institute, Conservation International, and the Woods Hole Oceanographic Institution. Our program has very positive interactions with, and support from, host country institutions, and through our outreach efforts we continue to improve the perceived value of biodiversity by Panamanians. The two collaborating companies (Novartis and Dow AgroSciences), one focused on pharmaceuticals and the other on agrochemicals, provide additional biotesting, financial and training resources, as well as a mechanism for the development of promising materials. All collection and bioassay information is maintained on a web database, and this insures excellent access by all team members as well as host country and US government partners. A well-developed set of legal documents assures a highly beneficial plan for intellectual property and benefit sharing with Panama.